Influence of marrow erythropoietic activity on serum erythropoietin levels after autologous hematopoietic stem cell transplantation

Abstract

Background and objective: Serum erythropoietin (sEpo) concentration depends primarily on the rate of renal production in response to hypoxia. However, sEpo levels increase inappropriately after conditioning for autologous stem cell transplantation (ASCT) before progressively returning to adequate levels. We investigated the possible influence of erythropoietic activity on these observations.

Design and methods: Forty patients undergoing an ASCT, 8 with bone marrow (BMT) and 32 with peripheral blood stem cells (PBSC), were separated into 3 groups. Group 1 was formed of the 8 BMT patients (median time to 1% reticulocytes: 39 days), group 2 of 16 PBSC patients with relatively slow erythroid engraftment (> or = 15 days to 1% reticulocytes, median 19 days) and group 3 of 16 PBSC patients with prompt erythroid recovery (< 15 days to 1% reticulocytes, median 13 days). Marrow erythroid activity was assessed by serum transferrin receptor levels (sTfR). Serum Epo (sEpo) levels were expressed in relation to the degree of anemia as observed/predicted (O/P) ratios of (O/P) log (sEpo).

Results: Serum sTfR levels decreased by more than 50% in all 3 groups after conditioning, reaching their nadir on day 7. Nadir values doubled by day 28 in group 3, day 60 in group 2, but not within 100 days in group 1. O/P sEpo ratios increased inappropriately in all 3 groups after conditioning but then declined at very differing speeds in the 3 groups. In group 1, ratios remained above 1.10 through to day 28 and above 1.00 through to day 42, before leveling off at around 1.00 thereafter. In group 2, ratios remained above 1.00 through to day 14, than decreased to a minimum of 0.89 by day 42 before returning to 1.00 by day 100. In group 3, ratios decreased to 0.84 by day 21 and remained below 0.90 thereafter.

Interpretation and conclusions: We conclude that sEpo levels are not only influenced by tissue oxygenation but also depend on the mass of erythroid precursors in the bone marrow. This may be the main explanation for the observed changes in sEpo levels during ASCT.